NOTCH1 and neoplasm: Mutation in the Kras affects the RAS/MAPK pathway, resulting in uncontrolled cell proliferation15 Deletion of Trp53 results in genetic instability.16 Constitutively active truncated Notch1 intracellular domain “N1icd” drives KPN toward an immunosuppressive TGF-β-driven tumor microenvironment (TME).14 The combination generates tumors in the intestine with metastases in the liver and adjoining organs.14 Late-stage liver metastasis is modeled using the intra-splenic transplantation.